User login
JAK2 inhibitor could treat B-ALL
Photo courtesy of the
Dana-Farber Cancer Institute
A type II JAK2 inhibitor has shown activity against B-cell acute lymphoblastic leukemia (B-ALL) in preclinical experiments.
The inhibitor, known as CHZ868, works by binding JAK2 into a tightly clenched position, which prevents the protein from functioning.
Researchers tested CHZ868 in samples from patients with CRLF2-rearranged B-ALL, in mice with the disease, and in mice implanted with human B-ALL tissue.
“In each case, we saw good activity: leukemia cells died, JAK2 signaling was suspended, and survival rates increased,” said David Weinstock, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts.
“When we combined CHZ868 with the steroid dexamethasone, the killing of leukemia cells was much more extensive, and the animals lived longer than they did with CHZ868 alone.”
Dr Weinstock and his colleagues reported these results in Cancer Cell. Some of the researchers involved in this work are employees of, or have received research funding from, Novartis.
The team found that CHZ868 inhibited JAK2 signaling in B-ALL, both in vitro and in vivo. CHZ868 could overcome persistent JAK2 signaling where type I JAK2 inhibitors (BSK805 and BVB808) could not.
However, the researchers also identified a mutation—JAK2 L884P—that conferred resistance to CHZ868 and another type II JAK2 inhibitor, BBT594.
Nevertheless, CHZ868 suppressed the growth of CRLF2-rearranged human B-ALL cells and improved survival in mice with human or murine B-ALL.
CHZ868 worked synergistically with dexamethasone to induce apoptosis in JAK2-dependent B-ALL. The combination also improved survival in mice with B-ALL, when compared to either dexamethasone or CHZ868 alone.
The researchers noted that, when given at 30 mg/kg/day, CHZ868 was tolerated in NSG mice for up to 25 days and in immunocompetent mice for up to 44 days. And the drug had “essentially no effects” on peripheral blood counts.
This result and the tolerability of dexamethasone make CHZ868 and dexamethasone a “particularly attractive” combination that should be investigated in clinical trials, the team said.
They also speculated that CHZ868 or other type II JAK2 inhibitors could prove effective against malignancies other than B-ALL.
“JAK2 abnormalities are found in some cases of triple-negative breast cancer and Hodgkin lymphoma,” Dr Weinstock noted. “The success of CHZ868 in B-ALL suggests that it, or a compound that works by a similar mechanism, may also be effective in these cancers.” 
Photo courtesy of the
Dana-Farber Cancer Institute
A type II JAK2 inhibitor has shown activity against B-cell acute lymphoblastic leukemia (B-ALL) in preclinical experiments.
The inhibitor, known as CHZ868, works by binding JAK2 into a tightly clenched position, which prevents the protein from functioning.
Researchers tested CHZ868 in samples from patients with CRLF2-rearranged B-ALL, in mice with the disease, and in mice implanted with human B-ALL tissue.
“In each case, we saw good activity: leukemia cells died, JAK2 signaling was suspended, and survival rates increased,” said David Weinstock, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts.
“When we combined CHZ868 with the steroid dexamethasone, the killing of leukemia cells was much more extensive, and the animals lived longer than they did with CHZ868 alone.”
Dr Weinstock and his colleagues reported these results in Cancer Cell. Some of the researchers involved in this work are employees of, or have received research funding from, Novartis.
The team found that CHZ868 inhibited JAK2 signaling in B-ALL, both in vitro and in vivo. CHZ868 could overcome persistent JAK2 signaling where type I JAK2 inhibitors (BSK805 and BVB808) could not.
However, the researchers also identified a mutation—JAK2 L884P—that conferred resistance to CHZ868 and another type II JAK2 inhibitor, BBT594.
Nevertheless, CHZ868 suppressed the growth of CRLF2-rearranged human B-ALL cells and improved survival in mice with human or murine B-ALL.
CHZ868 worked synergistically with dexamethasone to induce apoptosis in JAK2-dependent B-ALL. The combination also improved survival in mice with B-ALL, when compared to either dexamethasone or CHZ868 alone.
The researchers noted that, when given at 30 mg/kg/day, CHZ868 was tolerated in NSG mice for up to 25 days and in immunocompetent mice for up to 44 days. And the drug had “essentially no effects” on peripheral blood counts.
This result and the tolerability of dexamethasone make CHZ868 and dexamethasone a “particularly attractive” combination that should be investigated in clinical trials, the team said.
They also speculated that CHZ868 or other type II JAK2 inhibitors could prove effective against malignancies other than B-ALL.
“JAK2 abnormalities are found in some cases of triple-negative breast cancer and Hodgkin lymphoma,” Dr Weinstock noted. “The success of CHZ868 in B-ALL suggests that it, or a compound that works by a similar mechanism, may also be effective in these cancers.”
Photo courtesy of the
Dana-Farber Cancer Institute
A type II JAK2 inhibitor has shown activity against B-cell acute lymphoblastic leukemia (B-ALL) in preclinical experiments.
The inhibitor, known as CHZ868, works by binding JAK2 into a tightly clenched position, which prevents the protein from functioning.
Researchers tested CHZ868 in samples from patients with CRLF2-rearranged B-ALL, in mice with the disease, and in mice implanted with human B-ALL tissue.
“In each case, we saw good activity: leukemia cells died, JAK2 signaling was suspended, and survival rates increased,” said David Weinstock, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts.
“When we combined CHZ868 with the steroid dexamethasone, the killing of leukemia cells was much more extensive, and the animals lived longer than they did with CHZ868 alone.”
Dr Weinstock and his colleagues reported these results in Cancer Cell. Some of the researchers involved in this work are employees of, or have received research funding from, Novartis.
The team found that CHZ868 inhibited JAK2 signaling in B-ALL, both in vitro and in vivo. CHZ868 could overcome persistent JAK2 signaling where type I JAK2 inhibitors (BSK805 and BVB808) could not.
However, the researchers also identified a mutation—JAK2 L884P—that conferred resistance to CHZ868 and another type II JAK2 inhibitor, BBT594.
Nevertheless, CHZ868 suppressed the growth of CRLF2-rearranged human B-ALL cells and improved survival in mice with human or murine B-ALL.
CHZ868 worked synergistically with dexamethasone to induce apoptosis in JAK2-dependent B-ALL. The combination also improved survival in mice with B-ALL, when compared to either dexamethasone or CHZ868 alone.
The researchers noted that, when given at 30 mg/kg/day, CHZ868 was tolerated in NSG mice for up to 25 days and in immunocompetent mice for up to 44 days. And the drug had “essentially no effects” on peripheral blood counts.
This result and the tolerability of dexamethasone make CHZ868 and dexamethasone a “particularly attractive” combination that should be investigated in clinical trials, the team said.
They also speculated that CHZ868 or other type II JAK2 inhibitors could prove effective against malignancies other than B-ALL.
“JAK2 abnormalities are found in some cases of triple-negative breast cancer and Hodgkin lymphoma,” Dr Weinstock noted. “The success of CHZ868 in B-ALL suggests that it, or a compound that works by a similar mechanism, may also be effective in these cancers.”
Length of cell-cycle phase affects HSC function
in the bone marrow
Shortening the G1 phase of the cell cycle can improve the production and function of hematopoietic stem cells (HSCs), according to research published in the Journal of Experimental Medicine.
When investigators shortened the G1 phase in human HSCs, they found the cells were better able to resist differentiation in vitro and exhibited enhanced engraftment in vivo.
However, these benefits only occurred when the team shortened the early phase of G1, not the late phase.
Claudia Waskow, PhD, of Technische Universitaet Dresden in Germany, and her colleagues conducted this research to determine whether the function of human HSCs is controlled by the kinetics of cell-cycle progression.
The investigators knew that the body’s pool of HSCs is maintained through self-renewing divisions tightly regulated by enzymatically active cyclin (CCN)/cyclin-dependent kinase (CDK) complexes.
So they enforced expression of functional CCND1–CDK4 complexes, which are important for progression through the early G1 phase of the cell cycle, and CCNE1–CDK2 complexes, which are key in the transition from the G1 phase to the S phase.
Overexpression of CCND1–CDK4 complexes (also referred to as elevated 4D) promoted the transit from G0 to G1 and successfully shortened the G1 phase. However, the total length of the cell cycle did not change much, as the G2 or M phase was prolonged slightly.
The investigators also found that elevated 4D levels protected HSCs from differentiation-inducing signals in vitro and provided a “competitive advantage” in vivo.
When they transplanted HSCs with elevated 4D into mice, the team observed improved donor-leukocyte engraftment but no increase in the HSC pool. They said the improvement in engraftment was based on an elevated output of myeloid cells.
In contrast to elevated 4D, overexpression of CCNE1–CDK2 (also referred to as elevated 2E) conferred detrimental effects. Elevated 2E did accelerate cell-cycle progression, but it led to the loss of functional HSCs and poor engraftment.
The investigators said a large proportion of cells with elevated 2E contained fragmented DNA and underwent apoptosis after transduction.
In addition, many HSCs with elevated 2E exited G0 and shifted to the S–G2–M phases of the cell cycle. The G1 phase was significantly shortened, and the time HSCs spent in each cycle was reduced.
Dr Waskow and her colleagues said these results suggest transit velocity through the early and late G1 phase is an important regulator of HSC function and therefore makes an essential contribution to the maintenance of hematopoiesis.
Furthermore, alterations of G1 transition kinetics may be the basis for functional defects observed in HSCs from old mice or elderly humans.
in the bone marrow
Shortening the G1 phase of the cell cycle can improve the production and function of hematopoietic stem cells (HSCs), according to research published in the Journal of Experimental Medicine.
When investigators shortened the G1 phase in human HSCs, they found the cells were better able to resist differentiation in vitro and exhibited enhanced engraftment in vivo.
However, these benefits only occurred when the team shortened the early phase of G1, not the late phase.
Claudia Waskow, PhD, of Technische Universitaet Dresden in Germany, and her colleagues conducted this research to determine whether the function of human HSCs is controlled by the kinetics of cell-cycle progression.
The investigators knew that the body’s pool of HSCs is maintained through self-renewing divisions tightly regulated by enzymatically active cyclin (CCN)/cyclin-dependent kinase (CDK) complexes.
So they enforced expression of functional CCND1–CDK4 complexes, which are important for progression through the early G1 phase of the cell cycle, and CCNE1–CDK2 complexes, which are key in the transition from the G1 phase to the S phase.
Overexpression of CCND1–CDK4 complexes (also referred to as elevated 4D) promoted the transit from G0 to G1 and successfully shortened the G1 phase. However, the total length of the cell cycle did not change much, as the G2 or M phase was prolonged slightly.
The investigators also found that elevated 4D levels protected HSCs from differentiation-inducing signals in vitro and provided a “competitive advantage” in vivo.
When they transplanted HSCs with elevated 4D into mice, the team observed improved donor-leukocyte engraftment but no increase in the HSC pool. They said the improvement in engraftment was based on an elevated output of myeloid cells.
In contrast to elevated 4D, overexpression of CCNE1–CDK2 (also referred to as elevated 2E) conferred detrimental effects. Elevated 2E did accelerate cell-cycle progression, but it led to the loss of functional HSCs and poor engraftment.
The investigators said a large proportion of cells with elevated 2E contained fragmented DNA and underwent apoptosis after transduction.
In addition, many HSCs with elevated 2E exited G0 and shifted to the S–G2–M phases of the cell cycle. The G1 phase was significantly shortened, and the time HSCs spent in each cycle was reduced.
Dr Waskow and her colleagues said these results suggest transit velocity through the early and late G1 phase is an important regulator of HSC function and therefore makes an essential contribution to the maintenance of hematopoiesis.
Furthermore, alterations of G1 transition kinetics may be the basis for functional defects observed in HSCs from old mice or elderly humans.
in the bone marrow
Shortening the G1 phase of the cell cycle can improve the production and function of hematopoietic stem cells (HSCs), according to research published in the Journal of Experimental Medicine.
When investigators shortened the G1 phase in human HSCs, they found the cells were better able to resist differentiation in vitro and exhibited enhanced engraftment in vivo.
However, these benefits only occurred when the team shortened the early phase of G1, not the late phase.
Claudia Waskow, PhD, of Technische Universitaet Dresden in Germany, and her colleagues conducted this research to determine whether the function of human HSCs is controlled by the kinetics of cell-cycle progression.
The investigators knew that the body’s pool of HSCs is maintained through self-renewing divisions tightly regulated by enzymatically active cyclin (CCN)/cyclin-dependent kinase (CDK) complexes.
So they enforced expression of functional CCND1–CDK4 complexes, which are important for progression through the early G1 phase of the cell cycle, and CCNE1–CDK2 complexes, which are key in the transition from the G1 phase to the S phase.
Overexpression of CCND1–CDK4 complexes (also referred to as elevated 4D) promoted the transit from G0 to G1 and successfully shortened the G1 phase. However, the total length of the cell cycle did not change much, as the G2 or M phase was prolonged slightly.
The investigators also found that elevated 4D levels protected HSCs from differentiation-inducing signals in vitro and provided a “competitive advantage” in vivo.
When they transplanted HSCs with elevated 4D into mice, the team observed improved donor-leukocyte engraftment but no increase in the HSC pool. They said the improvement in engraftment was based on an elevated output of myeloid cells.
In contrast to elevated 4D, overexpression of CCNE1–CDK2 (also referred to as elevated 2E) conferred detrimental effects. Elevated 2E did accelerate cell-cycle progression, but it led to the loss of functional HSCs and poor engraftment.
The investigators said a large proportion of cells with elevated 2E contained fragmented DNA and underwent apoptosis after transduction.
In addition, many HSCs with elevated 2E exited G0 and shifted to the S–G2–M phases of the cell cycle. The G1 phase was significantly shortened, and the time HSCs spent in each cycle was reduced.
Dr Waskow and her colleagues said these results suggest transit velocity through the early and late G1 phase is an important regulator of HSC function and therefore makes an essential contribution to the maintenance of hematopoiesis.
Furthermore, alterations of G1 transition kinetics may be the basis for functional defects observed in HSCs from old mice or elderly humans.
ASCO updates guideline on CSFs
The American Society of Clinical Oncology (ASCO) has updated its clinical practice guideline on hematopoietic colony-stimulating factors (CSFs).
The guideline includes recommendations on the use of CSFs in the context of lymphoma, solid tumor malignancies, pediatric leukemia, and hematopoietic stem cell transplant.
There are no recommendations pertaining to adults with acute myeloid leukemia or myelodysplastic syndromes.
ASCO’s previous guideline on CSFs was issued in 2006. For the update, an ASCO expert panel conducted a formal systematic review of relevant articles from the medical literature published from October 2005 through September 2014.
Key recommendations from the resulting guideline are as follows.
Pegfilgrastim, filgrastim, tbo-filgrastim, and filgrastim-sndz (and other biosimilars, as they become available) can be used for the prevention of treatment-related febrile neutropenia.
For patients with lymphomas or solid tumors, primary prophylaxis with a CSF should be given during all cycles of chemotherapy in patients who have an approximately 20% or higher risk for febrile neutropenia on the basis of patient-, disease-, and treatment-related factors.
However, clinicians should also consider using chemotherapy regimens that do not require CSF administration but are as effective as regimens that do require a CSF.
Patients with lymphomas or solid tumors should receive secondary febrile neutropenia prophylaxis with a CSF if they experienced a neutropenic complication from a previous cycle of chemotherapy (for which they did not receive primary prophylaxis) when a reduced dose or treatment delay may compromise disease-free survival, overall survival, or treatment outcome.
However, the guideline also says that, in many clinical situations, dose reductions or delays may be a reasonable alternative.
CSFs should not be routinely used for patients with neutropenia who are afebrile or as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia.
Dose-dense regimens with CSF support should only be used within an appropriately designed clinical trial or if use of the regimen is supported by convincing efficacy data. The guideline says that, for non-Hodgkin lymphoma, data on the value of dose-dense regimens with CSF support are limited and conflicting.
In the context of transplant, CSFs may be used alone, after chemotherapy, or in combination with plerixafor to mobilize peripheral blood stem cells. To reduce the duration of severe neutropenia, CSFs should be administered after autologous stem cell transplant and may be administered after allogeneic stem cell transplant.
CSFs should be avoided in patients receiving concomitant chemotherapy and radiation, particularly involving the mediastinum. CSFs may be considered in patients receiving radiation alone if the clinician expects prolonged treatment delays due to neutropenia.
Patients who are exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death resulting from injury to other organs, should promptly receive CSFs or pegylated granulocyte CSFs.
Clinicians should consider prophylactic CSF for patients with diffuse aggressive lymphoma who are 65 or older and are receiving curative chemotherapy (R-CHOP), particularly if they have comorbidities.
The guideline also says the use of CSFs in pediatric patients will almost always be guided by clinical protocols. But CSFs should not be used in pediatric patients with nonrelapsed acute lymphoblastic leukemia or nonrelapsed acute myeloid leukemia who do not have an infection.
For more details, see the complete guideline. ASCO said it encourages feedback on its guidelines from oncologists, practitioners, and patients through the ASCO Guidelines Wiki.
The American Society of Clinical Oncology (ASCO) has updated its clinical practice guideline on hematopoietic colony-stimulating factors (CSFs).
The guideline includes recommendations on the use of CSFs in the context of lymphoma, solid tumor malignancies, pediatric leukemia, and hematopoietic stem cell transplant.
There are no recommendations pertaining to adults with acute myeloid leukemia or myelodysplastic syndromes.
ASCO’s previous guideline on CSFs was issued in 2006. For the update, an ASCO expert panel conducted a formal systematic review of relevant articles from the medical literature published from October 2005 through September 2014.
Key recommendations from the resulting guideline are as follows.
Pegfilgrastim, filgrastim, tbo-filgrastim, and filgrastim-sndz (and other biosimilars, as they become available) can be used for the prevention of treatment-related febrile neutropenia.
For patients with lymphomas or solid tumors, primary prophylaxis with a CSF should be given during all cycles of chemotherapy in patients who have an approximately 20% or higher risk for febrile neutropenia on the basis of patient-, disease-, and treatment-related factors.
However, clinicians should also consider using chemotherapy regimens that do not require CSF administration but are as effective as regimens that do require a CSF.
Patients with lymphomas or solid tumors should receive secondary febrile neutropenia prophylaxis with a CSF if they experienced a neutropenic complication from a previous cycle of chemotherapy (for which they did not receive primary prophylaxis) when a reduced dose or treatment delay may compromise disease-free survival, overall survival, or treatment outcome.
However, the guideline also says that, in many clinical situations, dose reductions or delays may be a reasonable alternative.
CSFs should not be routinely used for patients with neutropenia who are afebrile or as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia.
Dose-dense regimens with CSF support should only be used within an appropriately designed clinical trial or if use of the regimen is supported by convincing efficacy data. The guideline says that, for non-Hodgkin lymphoma, data on the value of dose-dense regimens with CSF support are limited and conflicting.
In the context of transplant, CSFs may be used alone, after chemotherapy, or in combination with plerixafor to mobilize peripheral blood stem cells. To reduce the duration of severe neutropenia, CSFs should be administered after autologous stem cell transplant and may be administered after allogeneic stem cell transplant.
CSFs should be avoided in patients receiving concomitant chemotherapy and radiation, particularly involving the mediastinum. CSFs may be considered in patients receiving radiation alone if the clinician expects prolonged treatment delays due to neutropenia.
Patients who are exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death resulting from injury to other organs, should promptly receive CSFs or pegylated granulocyte CSFs.
Clinicians should consider prophylactic CSF for patients with diffuse aggressive lymphoma who are 65 or older and are receiving curative chemotherapy (R-CHOP), particularly if they have comorbidities.
The guideline also says the use of CSFs in pediatric patients will almost always be guided by clinical protocols. But CSFs should not be used in pediatric patients with nonrelapsed acute lymphoblastic leukemia or nonrelapsed acute myeloid leukemia who do not have an infection.
For more details, see the complete guideline. ASCO said it encourages feedback on its guidelines from oncologists, practitioners, and patients through the ASCO Guidelines Wiki.
The American Society of Clinical Oncology (ASCO) has updated its clinical practice guideline on hematopoietic colony-stimulating factors (CSFs).
The guideline includes recommendations on the use of CSFs in the context of lymphoma, solid tumor malignancies, pediatric leukemia, and hematopoietic stem cell transplant.
There are no recommendations pertaining to adults with acute myeloid leukemia or myelodysplastic syndromes.
ASCO’s previous guideline on CSFs was issued in 2006. For the update, an ASCO expert panel conducted a formal systematic review of relevant articles from the medical literature published from October 2005 through September 2014.
Key recommendations from the resulting guideline are as follows.
Pegfilgrastim, filgrastim, tbo-filgrastim, and filgrastim-sndz (and other biosimilars, as they become available) can be used for the prevention of treatment-related febrile neutropenia.
For patients with lymphomas or solid tumors, primary prophylaxis with a CSF should be given during all cycles of chemotherapy in patients who have an approximately 20% or higher risk for febrile neutropenia on the basis of patient-, disease-, and treatment-related factors.
However, clinicians should also consider using chemotherapy regimens that do not require CSF administration but are as effective as regimens that do require a CSF.
Patients with lymphomas or solid tumors should receive secondary febrile neutropenia prophylaxis with a CSF if they experienced a neutropenic complication from a previous cycle of chemotherapy (for which they did not receive primary prophylaxis) when a reduced dose or treatment delay may compromise disease-free survival, overall survival, or treatment outcome.
However, the guideline also says that, in many clinical situations, dose reductions or delays may be a reasonable alternative.
CSFs should not be routinely used for patients with neutropenia who are afebrile or as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia.
Dose-dense regimens with CSF support should only be used within an appropriately designed clinical trial or if use of the regimen is supported by convincing efficacy data. The guideline says that, for non-Hodgkin lymphoma, data on the value of dose-dense regimens with CSF support are limited and conflicting.
In the context of transplant, CSFs may be used alone, after chemotherapy, or in combination with plerixafor to mobilize peripheral blood stem cells. To reduce the duration of severe neutropenia, CSFs should be administered after autologous stem cell transplant and may be administered after allogeneic stem cell transplant.
CSFs should be avoided in patients receiving concomitant chemotherapy and radiation, particularly involving the mediastinum. CSFs may be considered in patients receiving radiation alone if the clinician expects prolonged treatment delays due to neutropenia.
Patients who are exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death resulting from injury to other organs, should promptly receive CSFs or pegylated granulocyte CSFs.
Clinicians should consider prophylactic CSF for patients with diffuse aggressive lymphoma who are 65 or older and are receiving curative chemotherapy (R-CHOP), particularly if they have comorbidities.
The guideline also says the use of CSFs in pediatric patients will almost always be guided by clinical protocols. But CSFs should not be used in pediatric patients with nonrelapsed acute lymphoblastic leukemia or nonrelapsed acute myeloid leukemia who do not have an infection.
For more details, see the complete guideline. ASCO said it encourages feedback on its guidelines from oncologists, practitioners, and patients through the ASCO Guidelines Wiki.
Restrictive transfusion may be safe for AUGIB
Photo by Elise Amendola
Results of a pilot study suggest a restrictive transfusion strategy may be safe for patients with acute upper gastrointestinal bleeding (AUGIB), but investigators say more research is needed.
In this study, known as TRIGGER, use of a restrictive transfusion strategy led to a 13% reduction in red blood cell (RBC) transfusions compared to the liberal strategy, but this difference was not statistically significant.
Likewise, there was no significant difference in clinical outcomes whether AUGIB patients received transfusions according to the restrictive strategy or the liberal one.
These results suggest a need for a large, randomized trial, according to investigators.
“If restrictive practice is proven to be safe in a large study, it could potentially safely reduce the use of red blood cell transfusions and produce cost savings . . . ,” said Vipul Jairath, MBChB, DPhil, of Oxford University Hospitals in the UK.
He and his colleagues conducted the TRIGGER trial and reported the results in The Lancet.
The study included 6 hospitals that had more than 20 AUGIB admissions monthly, more than 400 adult beds, 24-hour endoscopy, and onsite intensive care and surgery. Patients were eligible if they presented with new AUGIB (defined by hematemesis or melena) and were 18 or older. The only exclusion criterion was exsanguinating hemorrhage.
The investigators enrolled 936 patients—403 on the restrictive transfusion arm and 533 on the liberal arm. Patients in the restrictive arm were eligible to receive RBCs when their hemoglobin concentration fell below 80 g/L, with a post-transfusion target of 81-100 g/L.
Patients in the liberal arm were eligible for transfusion when their hemoglobin concentration fell below 100 g/L, with a post-transfusion target of 101-120 g/L. These thresholds were informed by UK transfusion practices.
Protocol adherence was 96% in the restrictive arm and 83% in the liberal arm. The mean last recorded hemoglobin concentration was 116 g/L for the restrictive arm and 118 g/L for the liberal arm.
The investigators noted that there was a 13% absolute reduction in the proportion of patients transfused in the restrictive arm, a reduction in the amount of RBCs transfused between the arms, and a separation in hemoglobin concentration between the arms, but none of these differences were significant.
In addition, there was no significant difference in clinical outcomes between the arms, although the trial was not powered to assess these outcomes.
All-cause mortality at day 28 was 7% in the liberal transfusion arm and 5% in the restrictive arm. The rate of serious adverse events at day 28 was 22% and 18%, respectively.
At hospital discharge, further bleeding had occurred in 6% of patients in the liberal arm and 4% in the restrictive arm. At day 28, further bleeding had occurred in 9% and 5%, respectively.
At discharge, thromboembolic or ischemic events had occurred in 5% of patients in the liberal arm and 3% in the restrictive arm. At day 28, these events had occurred in 7% and 4%, respectively.
At discharge, acute transfusion reactions had occurred in 2% of patients in the liberal arm and 1% in the restrictive arm, and infections had occurred in 24% and 26%, respectively.
By discharge, 38% of patients in the liberal arm and 32% in the restrictive arm had required some therapeutic intervention. Surgical or radiological intervention was required in 3% and 4%, respectively.
Considering these results, the investigators said the TRIGGER trial has paved the way for a phase 3 trial that could provide evidence to inform transfusion guidelines for patients with AUGIB.
Photo by Elise Amendola
Results of a pilot study suggest a restrictive transfusion strategy may be safe for patients with acute upper gastrointestinal bleeding (AUGIB), but investigators say more research is needed.
In this study, known as TRIGGER, use of a restrictive transfusion strategy led to a 13% reduction in red blood cell (RBC) transfusions compared to the liberal strategy, but this difference was not statistically significant.
Likewise, there was no significant difference in clinical outcomes whether AUGIB patients received transfusions according to the restrictive strategy or the liberal one.
These results suggest a need for a large, randomized trial, according to investigators.
“If restrictive practice is proven to be safe in a large study, it could potentially safely reduce the use of red blood cell transfusions and produce cost savings . . . ,” said Vipul Jairath, MBChB, DPhil, of Oxford University Hospitals in the UK.
He and his colleagues conducted the TRIGGER trial and reported the results in The Lancet.
The study included 6 hospitals that had more than 20 AUGIB admissions monthly, more than 400 adult beds, 24-hour endoscopy, and onsite intensive care and surgery. Patients were eligible if they presented with new AUGIB (defined by hematemesis or melena) and were 18 or older. The only exclusion criterion was exsanguinating hemorrhage.
The investigators enrolled 936 patients—403 on the restrictive transfusion arm and 533 on the liberal arm. Patients in the restrictive arm were eligible to receive RBCs when their hemoglobin concentration fell below 80 g/L, with a post-transfusion target of 81-100 g/L.
Patients in the liberal arm were eligible for transfusion when their hemoglobin concentration fell below 100 g/L, with a post-transfusion target of 101-120 g/L. These thresholds were informed by UK transfusion practices.
Protocol adherence was 96% in the restrictive arm and 83% in the liberal arm. The mean last recorded hemoglobin concentration was 116 g/L for the restrictive arm and 118 g/L for the liberal arm.
The investigators noted that there was a 13% absolute reduction in the proportion of patients transfused in the restrictive arm, a reduction in the amount of RBCs transfused between the arms, and a separation in hemoglobin concentration between the arms, but none of these differences were significant.
In addition, there was no significant difference in clinical outcomes between the arms, although the trial was not powered to assess these outcomes.
All-cause mortality at day 28 was 7% in the liberal transfusion arm and 5% in the restrictive arm. The rate of serious adverse events at day 28 was 22% and 18%, respectively.
At hospital discharge, further bleeding had occurred in 6% of patients in the liberal arm and 4% in the restrictive arm. At day 28, further bleeding had occurred in 9% and 5%, respectively.
At discharge, thromboembolic or ischemic events had occurred in 5% of patients in the liberal arm and 3% in the restrictive arm. At day 28, these events had occurred in 7% and 4%, respectively.
At discharge, acute transfusion reactions had occurred in 2% of patients in the liberal arm and 1% in the restrictive arm, and infections had occurred in 24% and 26%, respectively.
By discharge, 38% of patients in the liberal arm and 32% in the restrictive arm had required some therapeutic intervention. Surgical or radiological intervention was required in 3% and 4%, respectively.
Considering these results, the investigators said the TRIGGER trial has paved the way for a phase 3 trial that could provide evidence to inform transfusion guidelines for patients with AUGIB.
Photo by Elise Amendola
Results of a pilot study suggest a restrictive transfusion strategy may be safe for patients with acute upper gastrointestinal bleeding (AUGIB), but investigators say more research is needed.
In this study, known as TRIGGER, use of a restrictive transfusion strategy led to a 13% reduction in red blood cell (RBC) transfusions compared to the liberal strategy, but this difference was not statistically significant.
Likewise, there was no significant difference in clinical outcomes whether AUGIB patients received transfusions according to the restrictive strategy or the liberal one.
These results suggest a need for a large, randomized trial, according to investigators.
“If restrictive practice is proven to be safe in a large study, it could potentially safely reduce the use of red blood cell transfusions and produce cost savings . . . ,” said Vipul Jairath, MBChB, DPhil, of Oxford University Hospitals in the UK.
He and his colleagues conducted the TRIGGER trial and reported the results in The Lancet.
The study included 6 hospitals that had more than 20 AUGIB admissions monthly, more than 400 adult beds, 24-hour endoscopy, and onsite intensive care and surgery. Patients were eligible if they presented with new AUGIB (defined by hematemesis or melena) and were 18 or older. The only exclusion criterion was exsanguinating hemorrhage.
The investigators enrolled 936 patients—403 on the restrictive transfusion arm and 533 on the liberal arm. Patients in the restrictive arm were eligible to receive RBCs when their hemoglobin concentration fell below 80 g/L, with a post-transfusion target of 81-100 g/L.
Patients in the liberal arm were eligible for transfusion when their hemoglobin concentration fell below 100 g/L, with a post-transfusion target of 101-120 g/L. These thresholds were informed by UK transfusion practices.
Protocol adherence was 96% in the restrictive arm and 83% in the liberal arm. The mean last recorded hemoglobin concentration was 116 g/L for the restrictive arm and 118 g/L for the liberal arm.
The investigators noted that there was a 13% absolute reduction in the proportion of patients transfused in the restrictive arm, a reduction in the amount of RBCs transfused between the arms, and a separation in hemoglobin concentration between the arms, but none of these differences were significant.
In addition, there was no significant difference in clinical outcomes between the arms, although the trial was not powered to assess these outcomes.
All-cause mortality at day 28 was 7% in the liberal transfusion arm and 5% in the restrictive arm. The rate of serious adverse events at day 28 was 22% and 18%, respectively.
At hospital discharge, further bleeding had occurred in 6% of patients in the liberal arm and 4% in the restrictive arm. At day 28, further bleeding had occurred in 9% and 5%, respectively.
At discharge, thromboembolic or ischemic events had occurred in 5% of patients in the liberal arm and 3% in the restrictive arm. At day 28, these events had occurred in 7% and 4%, respectively.
At discharge, acute transfusion reactions had occurred in 2% of patients in the liberal arm and 1% in the restrictive arm, and infections had occurred in 24% and 26%, respectively.
By discharge, 38% of patients in the liberal arm and 32% in the restrictive arm had required some therapeutic intervention. Surgical or radiological intervention was required in 3% and 4%, respectively.
Considering these results, the investigators said the TRIGGER trial has paved the way for a phase 3 trial that could provide evidence to inform transfusion guidelines for patients with AUGIB.
Drug worth pursuing as T-ALL therapy, researchers say
Photo courtesy of
Children’s Cancer Institute
A drug that previously fell short of expectations holds promise for treating T-cell acute lymphoblastic leukemia (T-ALL), according to researchers.
The drug, PR-104, was originally designed to target hypoxic cells in solid tumors, but it showed less activity than expected in clinical trials, and its development was suspended.
Now, preclinical research has shown that PR-104 can be activated by AKR1C3, an enzyme that is overexpressed in T-ALL.
The researchers described this work in Blood.
“We were so encouraged by our first results with PR-104 that we undertook additional studies which showed the drug to be preferentially active against T-ALL . . . ,” said study author Richard B. Lock, PhD, of the Children’s Cancer Institute in Sydney, New South Wales, Australia.
“We believe that PR-104 might be an effective drug for patients who have initially benefited from conventional treatment for T-ALL but who have subsequently relapsed.”
Developing PR-104: A rocky road
PR-104 is a phosphate ester of the nitrogen mustard prodrug PR-104A. It was invented by William R. Wilson, PhD, of the University of Auckland (UoA) in New Zealand, and licensed to a UoA start-up company called Proacta Inc.
In a phase 1 study of patients with solid tumor malignancies, PR-104 failed to produce responses. The drug did elicit responses in a phase 1/2 trial of patients with advanced ALL or acute myeloid leukemia, but results fell short of expectations, and Proacta suspended development of PR-104.
Another drug Proacta was developing, PR-610, also failed to meet expectations. Because of these setbacks, the company closed its doors.
“As a fragile start-up, [Proacta] could not survive two serial ‘failures’ in phase 1/2,” Dr Wilson said. “Arguably . . . , the failure was more to do with the attempt to develop these compounds without biomarker support . . . than lack of potential of the compounds. Interestingly, PR-610 has subsequently been licensed by UoA to Threshold Pharmaceuticals, who are continuing its development (with biomarker support) as TH-4000.”
“We have a more challenging problem with PR-104 because the original patents have lapsed thanks to the decision of the UoA to not maintain the national phase filings after Proacta pulled the plug. [However,] as a result of [Dr Lock’s] work, it is now clear that PR-104 has exciting potential in leukemias with high activity of
AKR1C3.”
Results in T-ALL
Dr Lock and his colleagues tested PR-104 in a panel of 7 patient-derived pediatric ALL xenografts. Two weekly doses of PR-104 at 200 mg/kg significantly delayed progression in both T-ALL (n=4) and B-cell-precursor (BCP) ALL (n=3) xenografts.
The delay ranged from 10.3 days to 59.2 days and was significantly longer for the T-ALL xenografts (P=0.03).
PR-104 produced objective responses in all 4 T-ALL xenografts, including 2 complete responses. The drug also produced complete responses in 2 of the 3 BCP-ALL xenografts, but the third exhibited progressive disease.
Additional experiments showed that AKR1C3 expression was significantly higher in T-ALL than BCP-ALL, and AKR1C3 was “a major determinant” of sensitivity to PR-104, both in vitro and in vivo.
The researchers confirmed this by overexpressing AKR1C3 in a resistant BCP-ALL xenograft. Once AKR1C3 was overexpressed, the team observed “dramatic sensitization” to PR-104.
The path ahead
Now, Dr Lock and his colleagues are trying to determine why T-ALL cells express high levels of AKR1C3.
“If we can work out what activates this enzyme in T cells, we might find a way of activating it in B cells, making the B-cell disease sensitive to the drug as well,” Dr Lock said. “Obviously, it would be ideal if we could extend this drug’s reach to include all acute lymphoblastic leukemia patients.”
“In the meantime, we can envisage using PR-104 to target highly aggressive T-ALLs that express high levels of AKR1C3. We are in the process of working with our clinician colleagues in Australia and the US to organize a clinical trial of PR-104 in T-ALL.”
Dr Wilson noted that finding a path forward for PR-104 will be challenging due to the lack of patent support.
“[But] there are two reasons that make me think it is worth trying to do so,” he said. “One is the proximate concern that there are kids with high-AKR1C3 leukemias (adults too) who could benefit from this opportunity. The other is that this problem links to a looming paradigm shift in drug development. As we dissect cancer based on molecular analysis . . . , the commercial model will have to change.”
“There will still be ‘blockbuster’ drugs from time to time that address very high numbers of cancers . . . , but my expectation is that most cancer control in the future will depend on understanding the peculiarities of individual tumors and matching these with drugs that exploit these features. PR-104 is currently stuck in the past but could be a poster child for that future.”
Photo courtesy of
Children’s Cancer Institute
A drug that previously fell short of expectations holds promise for treating T-cell acute lymphoblastic leukemia (T-ALL), according to researchers.
The drug, PR-104, was originally designed to target hypoxic cells in solid tumors, but it showed less activity than expected in clinical trials, and its development was suspended.
Now, preclinical research has shown that PR-104 can be activated by AKR1C3, an enzyme that is overexpressed in T-ALL.
The researchers described this work in Blood.
“We were so encouraged by our first results with PR-104 that we undertook additional studies which showed the drug to be preferentially active against T-ALL . . . ,” said study author Richard B. Lock, PhD, of the Children’s Cancer Institute in Sydney, New South Wales, Australia.
“We believe that PR-104 might be an effective drug for patients who have initially benefited from conventional treatment for T-ALL but who have subsequently relapsed.”
Developing PR-104: A rocky road
PR-104 is a phosphate ester of the nitrogen mustard prodrug PR-104A. It was invented by William R. Wilson, PhD, of the University of Auckland (UoA) in New Zealand, and licensed to a UoA start-up company called Proacta Inc.
In a phase 1 study of patients with solid tumor malignancies, PR-104 failed to produce responses. The drug did elicit responses in a phase 1/2 trial of patients with advanced ALL or acute myeloid leukemia, but results fell short of expectations, and Proacta suspended development of PR-104.
Another drug Proacta was developing, PR-610, also failed to meet expectations. Because of these setbacks, the company closed its doors.
“As a fragile start-up, [Proacta] could not survive two serial ‘failures’ in phase 1/2,” Dr Wilson said. “Arguably . . . , the failure was more to do with the attempt to develop these compounds without biomarker support . . . than lack of potential of the compounds. Interestingly, PR-610 has subsequently been licensed by UoA to Threshold Pharmaceuticals, who are continuing its development (with biomarker support) as TH-4000.”
“We have a more challenging problem with PR-104 because the original patents have lapsed thanks to the decision of the UoA to not maintain the national phase filings after Proacta pulled the plug. [However,] as a result of [Dr Lock’s] work, it is now clear that PR-104 has exciting potential in leukemias with high activity of
AKR1C3.”
Results in T-ALL
Dr Lock and his colleagues tested PR-104 in a panel of 7 patient-derived pediatric ALL xenografts. Two weekly doses of PR-104 at 200 mg/kg significantly delayed progression in both T-ALL (n=4) and B-cell-precursor (BCP) ALL (n=3) xenografts.
The delay ranged from 10.3 days to 59.2 days and was significantly longer for the T-ALL xenografts (P=0.03).
PR-104 produced objective responses in all 4 T-ALL xenografts, including 2 complete responses. The drug also produced complete responses in 2 of the 3 BCP-ALL xenografts, but the third exhibited progressive disease.
Additional experiments showed that AKR1C3 expression was significantly higher in T-ALL than BCP-ALL, and AKR1C3 was “a major determinant” of sensitivity to PR-104, both in vitro and in vivo.
The researchers confirmed this by overexpressing AKR1C3 in a resistant BCP-ALL xenograft. Once AKR1C3 was overexpressed, the team observed “dramatic sensitization” to PR-104.
The path ahead
Now, Dr Lock and his colleagues are trying to determine why T-ALL cells express high levels of AKR1C3.
“If we can work out what activates this enzyme in T cells, we might find a way of activating it in B cells, making the B-cell disease sensitive to the drug as well,” Dr Lock said. “Obviously, it would be ideal if we could extend this drug’s reach to include all acute lymphoblastic leukemia patients.”
“In the meantime, we can envisage using PR-104 to target highly aggressive T-ALLs that express high levels of AKR1C3. We are in the process of working with our clinician colleagues in Australia and the US to organize a clinical trial of PR-104 in T-ALL.”
Dr Wilson noted that finding a path forward for PR-104 will be challenging due to the lack of patent support.
“[But] there are two reasons that make me think it is worth trying to do so,” he said. “One is the proximate concern that there are kids with high-AKR1C3 leukemias (adults too) who could benefit from this opportunity. The other is that this problem links to a looming paradigm shift in drug development. As we dissect cancer based on molecular analysis . . . , the commercial model will have to change.”
“There will still be ‘blockbuster’ drugs from time to time that address very high numbers of cancers . . . , but my expectation is that most cancer control in the future will depend on understanding the peculiarities of individual tumors and matching these with drugs that exploit these features. PR-104 is currently stuck in the past but could be a poster child for that future.”
Photo courtesy of
Children’s Cancer Institute
A drug that previously fell short of expectations holds promise for treating T-cell acute lymphoblastic leukemia (T-ALL), according to researchers.
The drug, PR-104, was originally designed to target hypoxic cells in solid tumors, but it showed less activity than expected in clinical trials, and its development was suspended.
Now, preclinical research has shown that PR-104 can be activated by AKR1C3, an enzyme that is overexpressed in T-ALL.
The researchers described this work in Blood.
“We were so encouraged by our first results with PR-104 that we undertook additional studies which showed the drug to be preferentially active against T-ALL . . . ,” said study author Richard B. Lock, PhD, of the Children’s Cancer Institute in Sydney, New South Wales, Australia.
“We believe that PR-104 might be an effective drug for patients who have initially benefited from conventional treatment for T-ALL but who have subsequently relapsed.”
Developing PR-104: A rocky road
PR-104 is a phosphate ester of the nitrogen mustard prodrug PR-104A. It was invented by William R. Wilson, PhD, of the University of Auckland (UoA) in New Zealand, and licensed to a UoA start-up company called Proacta Inc.
In a phase 1 study of patients with solid tumor malignancies, PR-104 failed to produce responses. The drug did elicit responses in a phase 1/2 trial of patients with advanced ALL or acute myeloid leukemia, but results fell short of expectations, and Proacta suspended development of PR-104.
Another drug Proacta was developing, PR-610, also failed to meet expectations. Because of these setbacks, the company closed its doors.
“As a fragile start-up, [Proacta] could not survive two serial ‘failures’ in phase 1/2,” Dr Wilson said. “Arguably . . . , the failure was more to do with the attempt to develop these compounds without biomarker support . . . than lack of potential of the compounds. Interestingly, PR-610 has subsequently been licensed by UoA to Threshold Pharmaceuticals, who are continuing its development (with biomarker support) as TH-4000.”
“We have a more challenging problem with PR-104 because the original patents have lapsed thanks to the decision of the UoA to not maintain the national phase filings after Proacta pulled the plug. [However,] as a result of [Dr Lock’s] work, it is now clear that PR-104 has exciting potential in leukemias with high activity of
AKR1C3.”
Results in T-ALL
Dr Lock and his colleagues tested PR-104 in a panel of 7 patient-derived pediatric ALL xenografts. Two weekly doses of PR-104 at 200 mg/kg significantly delayed progression in both T-ALL (n=4) and B-cell-precursor (BCP) ALL (n=3) xenografts.
The delay ranged from 10.3 days to 59.2 days and was significantly longer for the T-ALL xenografts (P=0.03).
PR-104 produced objective responses in all 4 T-ALL xenografts, including 2 complete responses. The drug also produced complete responses in 2 of the 3 BCP-ALL xenografts, but the third exhibited progressive disease.
Additional experiments showed that AKR1C3 expression was significantly higher in T-ALL than BCP-ALL, and AKR1C3 was “a major determinant” of sensitivity to PR-104, both in vitro and in vivo.
The researchers confirmed this by overexpressing AKR1C3 in a resistant BCP-ALL xenograft. Once AKR1C3 was overexpressed, the team observed “dramatic sensitization” to PR-104.
The path ahead
Now, Dr Lock and his colleagues are trying to determine why T-ALL cells express high levels of AKR1C3.
“If we can work out what activates this enzyme in T cells, we might find a way of activating it in B cells, making the B-cell disease sensitive to the drug as well,” Dr Lock said. “Obviously, it would be ideal if we could extend this drug’s reach to include all acute lymphoblastic leukemia patients.”
“In the meantime, we can envisage using PR-104 to target highly aggressive T-ALLs that express high levels of AKR1C3. We are in the process of working with our clinician colleagues in Australia and the US to organize a clinical trial of PR-104 in T-ALL.”
Dr Wilson noted that finding a path forward for PR-104 will be challenging due to the lack of patent support.
“[But] there are two reasons that make me think it is worth trying to do so,” he said. “One is the proximate concern that there are kids with high-AKR1C3 leukemias (adults too) who could benefit from this opportunity. The other is that this problem links to a looming paradigm shift in drug development. As we dissect cancer based on molecular analysis . . . , the commercial model will have to change.”
“There will still be ‘blockbuster’ drugs from time to time that address very high numbers of cancers . . . , but my expectation is that most cancer control in the future will depend on understanding the peculiarities of individual tumors and matching these with drugs that exploit these features. PR-104 is currently stuck in the past but could be a poster child for that future.”
Adopting may be more difficult for cancer survivors
by Vera Kratochvil
Cancer survivors may face more challenges when trying to adopt a child than individuals without a history of cancer, according to a new study.
Investigators found the sizable upfront costs associated with adoption and requirements regarding a prospective parent’s health could work against cancer survivors trying to adopt.
However, the study also suggested that birth mothers might be receptive to cancer survivors as adoptive parents.
The research was published in Cancer.
Little is known about the rate at which cancer survivors successfully adopt a child or about their experiences during the adoption process. So Gwendolyn Quinn, PhD, of the Moffitt Cancer Center in Tampa, Florida, and her colleagues conducted a study to gain some insight.
The investigators asked oncology nurses who were participating in a training program to conduct interviews with adoption agencies. Seventy-seven nurses across 15 states provided summaries of their interviews.
The nurses reported that adoption fees ranged from $3000 to $75,000. They noted that the upfront costs of adoption could deter cancer survivors who already have “a huge financial burden” due to treatment costs.
Not all of the adoption agencies contacted kept records on whether prospective adoptive parents were cancer survivors. But agencies that did track this reported an average of 10 former cancer patients a year seeking adoption.
A few agencies reported that a cancer history in an adoptive parent could be discouraging for a birth mother. But most reported the opposite—that birth mothers might feel confident in choosing a parent who has overcome hardships and has an appreciation for life.
Agencies usually required prospective parents to provide a letter from a physician regarding their health and medical history. In some cases, agencies required cancer survivors to be disease-free for 5 years before they could adopt a child.
In addition, international adoptions had greater restrictions for prospective parents with a cancer history (compared to US adoptions).
Dr Quinn said these are potentially discriminatory practices akin to restricting employment opportunities for people with disabilities.
“[P]erhaps this data will bring to light the need for policy revisions in adoption processes . . . ,” she added.
by Vera Kratochvil
Cancer survivors may face more challenges when trying to adopt a child than individuals without a history of cancer, according to a new study.
Investigators found the sizable upfront costs associated with adoption and requirements regarding a prospective parent’s health could work against cancer survivors trying to adopt.
However, the study also suggested that birth mothers might be receptive to cancer survivors as adoptive parents.
The research was published in Cancer.
Little is known about the rate at which cancer survivors successfully adopt a child or about their experiences during the adoption process. So Gwendolyn Quinn, PhD, of the Moffitt Cancer Center in Tampa, Florida, and her colleagues conducted a study to gain some insight.
The investigators asked oncology nurses who were participating in a training program to conduct interviews with adoption agencies. Seventy-seven nurses across 15 states provided summaries of their interviews.
The nurses reported that adoption fees ranged from $3000 to $75,000. They noted that the upfront costs of adoption could deter cancer survivors who already have “a huge financial burden” due to treatment costs.
Not all of the adoption agencies contacted kept records on whether prospective adoptive parents were cancer survivors. But agencies that did track this reported an average of 10 former cancer patients a year seeking adoption.
A few agencies reported that a cancer history in an adoptive parent could be discouraging for a birth mother. But most reported the opposite—that birth mothers might feel confident in choosing a parent who has overcome hardships and has an appreciation for life.
Agencies usually required prospective parents to provide a letter from a physician regarding their health and medical history. In some cases, agencies required cancer survivors to be disease-free for 5 years before they could adopt a child.
In addition, international adoptions had greater restrictions for prospective parents with a cancer history (compared to US adoptions).
Dr Quinn said these are potentially discriminatory practices akin to restricting employment opportunities for people with disabilities.
“[P]erhaps this data will bring to light the need for policy revisions in adoption processes . . . ,” she added.
by Vera Kratochvil
Cancer survivors may face more challenges when trying to adopt a child than individuals without a history of cancer, according to a new study.
Investigators found the sizable upfront costs associated with adoption and requirements regarding a prospective parent’s health could work against cancer survivors trying to adopt.
However, the study also suggested that birth mothers might be receptive to cancer survivors as adoptive parents.
The research was published in Cancer.
Little is known about the rate at which cancer survivors successfully adopt a child or about their experiences during the adoption process. So Gwendolyn Quinn, PhD, of the Moffitt Cancer Center in Tampa, Florida, and her colleagues conducted a study to gain some insight.
The investigators asked oncology nurses who were participating in a training program to conduct interviews with adoption agencies. Seventy-seven nurses across 15 states provided summaries of their interviews.
The nurses reported that adoption fees ranged from $3000 to $75,000. They noted that the upfront costs of adoption could deter cancer survivors who already have “a huge financial burden” due to treatment costs.
Not all of the adoption agencies contacted kept records on whether prospective adoptive parents were cancer survivors. But agencies that did track this reported an average of 10 former cancer patients a year seeking adoption.
A few agencies reported that a cancer history in an adoptive parent could be discouraging for a birth mother. But most reported the opposite—that birth mothers might feel confident in choosing a parent who has overcome hardships and has an appreciation for life.
Agencies usually required prospective parents to provide a letter from a physician regarding their health and medical history. In some cases, agencies required cancer survivors to be disease-free for 5 years before they could adopt a child.
In addition, international adoptions had greater restrictions for prospective parents with a cancer history (compared to US adoptions).
Dr Quinn said these are potentially discriminatory practices akin to restricting employment opportunities for people with disabilities.
“[P]erhaps this data will bring to light the need for policy revisions in adoption processes . . . ,” she added.
Gene regulates HSPC frequency, function
Photo by Aaron Logan
A genome-wide association study conducted in mice has provided new insights regarding hematopoietic stem/progenitor cells (HSPCs).
Researchers screened more than 100 mouse strains and found great variation in the frequency of 3 HSPC subpopulations.
The team also showed that Hopx, a gene that was not known to influence HSPC biology, regulates the frequency and function of HSPCs.
The researchers recounted these findings in Stem Cell Reports.
Hooman Allayee, PhD, of the University of Southern California in Los Angeles, and his colleagues screened 108 strains of mice known as the hybrid mouse diversity panel.
The screen revealed 3 HSPC subpopulations whose frequency varied greatly among the different mouse strains. The frequency of these HSPCs—Lin-Sca-1+c-Kit+ (LSK) cells, LSKCD150-CD48- cells, and LSKCD150+CD48- cells—varied roughly 120-fold to 300-fold.
The researchers then found that these 3 cell populations were significantly correlated with each other and with certain hematologic parameters. There was a significant positive association between LSK cells and total white blood cell (P=0.005), monocyte (P<0.0001), and lymphocyte counts (P=0.04).
LSKCD150-CD48- cells had a significant negative correlation with lymphocyte (P=0.006) and monocyte counts (P=0.002) as well as a significant positive association with granulocyte counts (P=0.0002).
LSKCD150+CD48- cells had a significant positive correlation with total white blood cell count (P=0.02) and a significant negative association with mean corpuscular hemoglobin (P<0.001).
Additional experiments showed that the frequency and function of LSKCD150-CD48- cells were regulated by Hopx, but the gene did not appear to impact LSK or LSKCD150+CD48- cells.
Mice lacking the Hopx gene had significantly lower numbers of LSKCD150-CD48- cells than wild-type mice, but LSK and LSKCD150+CD48- counts were similar between Hopx-/- and wild-type mice.
The researchers also conducted competitive repopulation assays with HSCs from Hopx-/- and wild-type mice. HSCs from Hopx-/- mice had significantly impaired engraftment at 16 weeks after transplant, which extended to 24 weeks.
Dr Allayee and his colleagues said that identifying this new role for Hopx could have clinical implications, and this research suggests the hybrid mouse diversity panel can be used to find genes that would otherwise go unnoticed.
“This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Dr Allayee said.
Photo by Aaron Logan
A genome-wide association study conducted in mice has provided new insights regarding hematopoietic stem/progenitor cells (HSPCs).
Researchers screened more than 100 mouse strains and found great variation in the frequency of 3 HSPC subpopulations.
The team also showed that Hopx, a gene that was not known to influence HSPC biology, regulates the frequency and function of HSPCs.
The researchers recounted these findings in Stem Cell Reports.
Hooman Allayee, PhD, of the University of Southern California in Los Angeles, and his colleagues screened 108 strains of mice known as the hybrid mouse diversity panel.
The screen revealed 3 HSPC subpopulations whose frequency varied greatly among the different mouse strains. The frequency of these HSPCs—Lin-Sca-1+c-Kit+ (LSK) cells, LSKCD150-CD48- cells, and LSKCD150+CD48- cells—varied roughly 120-fold to 300-fold.
The researchers then found that these 3 cell populations were significantly correlated with each other and with certain hematologic parameters. There was a significant positive association between LSK cells and total white blood cell (P=0.005), monocyte (P<0.0001), and lymphocyte counts (P=0.04).
LSKCD150-CD48- cells had a significant negative correlation with lymphocyte (P=0.006) and monocyte counts (P=0.002) as well as a significant positive association with granulocyte counts (P=0.0002).
LSKCD150+CD48- cells had a significant positive correlation with total white blood cell count (P=0.02) and a significant negative association with mean corpuscular hemoglobin (P<0.001).
Additional experiments showed that the frequency and function of LSKCD150-CD48- cells were regulated by Hopx, but the gene did not appear to impact LSK or LSKCD150+CD48- cells.
Mice lacking the Hopx gene had significantly lower numbers of LSKCD150-CD48- cells than wild-type mice, but LSK and LSKCD150+CD48- counts were similar between Hopx-/- and wild-type mice.
The researchers also conducted competitive repopulation assays with HSCs from Hopx-/- and wild-type mice. HSCs from Hopx-/- mice had significantly impaired engraftment at 16 weeks after transplant, which extended to 24 weeks.
Dr Allayee and his colleagues said that identifying this new role for Hopx could have clinical implications, and this research suggests the hybrid mouse diversity panel can be used to find genes that would otherwise go unnoticed.
“This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Dr Allayee said.
Photo by Aaron Logan
A genome-wide association study conducted in mice has provided new insights regarding hematopoietic stem/progenitor cells (HSPCs).
Researchers screened more than 100 mouse strains and found great variation in the frequency of 3 HSPC subpopulations.
The team also showed that Hopx, a gene that was not known to influence HSPC biology, regulates the frequency and function of HSPCs.
The researchers recounted these findings in Stem Cell Reports.
Hooman Allayee, PhD, of the University of Southern California in Los Angeles, and his colleagues screened 108 strains of mice known as the hybrid mouse diversity panel.
The screen revealed 3 HSPC subpopulations whose frequency varied greatly among the different mouse strains. The frequency of these HSPCs—Lin-Sca-1+c-Kit+ (LSK) cells, LSKCD150-CD48- cells, and LSKCD150+CD48- cells—varied roughly 120-fold to 300-fold.
The researchers then found that these 3 cell populations were significantly correlated with each other and with certain hematologic parameters. There was a significant positive association between LSK cells and total white blood cell (P=0.005), monocyte (P<0.0001), and lymphocyte counts (P=0.04).
LSKCD150-CD48- cells had a significant negative correlation with lymphocyte (P=0.006) and monocyte counts (P=0.002) as well as a significant positive association with granulocyte counts (P=0.0002).
LSKCD150+CD48- cells had a significant positive correlation with total white blood cell count (P=0.02) and a significant negative association with mean corpuscular hemoglobin (P<0.001).
Additional experiments showed that the frequency and function of LSKCD150-CD48- cells were regulated by Hopx, but the gene did not appear to impact LSK or LSKCD150+CD48- cells.
Mice lacking the Hopx gene had significantly lower numbers of LSKCD150-CD48- cells than wild-type mice, but LSK and LSKCD150+CD48- counts were similar between Hopx-/- and wild-type mice.
The researchers also conducted competitive repopulation assays with HSCs from Hopx-/- and wild-type mice. HSCs from Hopx-/- mice had significantly impaired engraftment at 16 weeks after transplant, which extended to 24 weeks.
Dr Allayee and his colleagues said that identifying this new role for Hopx could have clinical implications, and this research suggests the hybrid mouse diversity panel can be used to find genes that would otherwise go unnoticed.
“This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Dr Allayee said.
Ibrutinib approved to treat WM in EU
The European Commission has granted marketing authorization for ibrutinib (Imbruvica) to treat Waldenstrom’s macroglobulinemia (WM).
The Bruton’s tyrosine kinase inhibitor is now approved to treat adults with WM who have received at least one prior therapy or as first-line treatment for patients considered unsuitable for chemo-immunotherapy.
Ibrutinib is the first therapy approved specifically for WM in the European Union (EU). The approval applies to all 28 EU member states, plus Iceland, Norway, and Liechtenstein.
Ibrutinib is already approved to treat WM in the US. The drug is also approved in the EU, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.
Janssen-Cilag International NV holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.
Phase 2 study
The European Commission’s approval of ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug (given at 420 mg once daily) in 63 patients with previously treated WM.
Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.
Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.
At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
The European Commission has granted marketing authorization for ibrutinib (Imbruvica) to treat Waldenstrom’s macroglobulinemia (WM).
The Bruton’s tyrosine kinase inhibitor is now approved to treat adults with WM who have received at least one prior therapy or as first-line treatment for patients considered unsuitable for chemo-immunotherapy.
Ibrutinib is the first therapy approved specifically for WM in the European Union (EU). The approval applies to all 28 EU member states, plus Iceland, Norway, and Liechtenstein.
Ibrutinib is already approved to treat WM in the US. The drug is also approved in the EU, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.
Janssen-Cilag International NV holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.
Phase 2 study
The European Commission’s approval of ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug (given at 420 mg once daily) in 63 patients with previously treated WM.
Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.
Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.
At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
The European Commission has granted marketing authorization for ibrutinib (Imbruvica) to treat Waldenstrom’s macroglobulinemia (WM).
The Bruton’s tyrosine kinase inhibitor is now approved to treat adults with WM who have received at least one prior therapy or as first-line treatment for patients considered unsuitable for chemo-immunotherapy.
Ibrutinib is the first therapy approved specifically for WM in the European Union (EU). The approval applies to all 28 EU member states, plus Iceland, Norway, and Liechtenstein.
Ibrutinib is already approved to treat WM in the US. The drug is also approved in the EU, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.
Janssen-Cilag International NV holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.
Phase 2 study
The European Commission’s approval of ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug (given at 420 mg once daily) in 63 patients with previously treated WM.
Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.
Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.
At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
Transcription factor promotes MM progression
rim of a bone spicule (pink)
New research indicates that multiple myeloma (MM) cells can “disguise” themselves as bone cells to elude the immune system, a trick that enables MM progression.
Investigators found evidence suggesting that MM cells mimic bone-marrow-resident cells by expressing bone-related genes, and this process is driven by overexpression of Runx2, a transcription factor that regulates bone formation.
“[R]unx2 overexpression can give multiple myeloma cells a bone-cell-like phenotype,” said Yang Yang, MD, PhD, of the University of Alabama at Birmingham.
“When the multiple myeloma cells come to the new bone sites, the bone immune cells think, ‘This is one of our neighbor cells,’ and therefore do not eliminate them. The bone immune cells do not recognize these cells as strangers.”
Dr Yang and her colleagues explained this phenomenon in Blood.
The investigators first conducted in vitro experiments and found that Runx2 expression in MM cells does not affect proliferation, but it does increase the cells’ invasiveness.
The team then used molecular genetic techniques to increase or decrease the expression of Runx2 in MM cells in vivo. They found that Runx2 overexpression promoted tumor growth and progression in mice. And mice with decreased Runx2 expression had less tumor growth and disease spread than control mice.
Further investigation revealed that Runx2 overexpression activates the Akt/β-catenin/survivin signaling pathway in MM cells. This is a different pathway than the one activated by Runx2 in solid tumors.
Downstream of the signaling pathway, Runx2 overexpression led to overexpression of bone-related genes, including genes expressed by osteoblasts, osteoclasts, and osteocytes.
Overexpression of Runx2 also enhanced secretion of soluble factors—including cytokines and growth factors—that aid tumor progression and metastasis.
In their final experiments, the investigators looked at Runx2 expression in human samples.
The team compared samples from 14 healthy bone marrow donors, 35 MM patients, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS). Runx2 levels were significantly higher in MM cells than in plasma cells from normal and MGUS samples.
The investigators also assessed Runx2 expression in a larger group of 351 newly diagnosed MM patients. Runx2 levels were significantly higher in patients who had a high risk of early disease-related death. The risk of death was determined by an existing gene expression profile test.
“This suggests that Runx2 levels in myeloma cells may be a gene predictor of a patient’s prognosis, good or bad,” Dr Yang said.
She and her colleagues also believe that targeting Runx2 expression could be a feasible strategy for treating aggressive MM.
rim of a bone spicule (pink)
New research indicates that multiple myeloma (MM) cells can “disguise” themselves as bone cells to elude the immune system, a trick that enables MM progression.
Investigators found evidence suggesting that MM cells mimic bone-marrow-resident cells by expressing bone-related genes, and this process is driven by overexpression of Runx2, a transcription factor that regulates bone formation.
“[R]unx2 overexpression can give multiple myeloma cells a bone-cell-like phenotype,” said Yang Yang, MD, PhD, of the University of Alabama at Birmingham.
“When the multiple myeloma cells come to the new bone sites, the bone immune cells think, ‘This is one of our neighbor cells,’ and therefore do not eliminate them. The bone immune cells do not recognize these cells as strangers.”
Dr Yang and her colleagues explained this phenomenon in Blood.
The investigators first conducted in vitro experiments and found that Runx2 expression in MM cells does not affect proliferation, but it does increase the cells’ invasiveness.
The team then used molecular genetic techniques to increase or decrease the expression of Runx2 in MM cells in vivo. They found that Runx2 overexpression promoted tumor growth and progression in mice. And mice with decreased Runx2 expression had less tumor growth and disease spread than control mice.
Further investigation revealed that Runx2 overexpression activates the Akt/β-catenin/survivin signaling pathway in MM cells. This is a different pathway than the one activated by Runx2 in solid tumors.
Downstream of the signaling pathway, Runx2 overexpression led to overexpression of bone-related genes, including genes expressed by osteoblasts, osteoclasts, and osteocytes.
Overexpression of Runx2 also enhanced secretion of soluble factors—including cytokines and growth factors—that aid tumor progression and metastasis.
In their final experiments, the investigators looked at Runx2 expression in human samples.
The team compared samples from 14 healthy bone marrow donors, 35 MM patients, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS). Runx2 levels were significantly higher in MM cells than in plasma cells from normal and MGUS samples.
The investigators also assessed Runx2 expression in a larger group of 351 newly diagnosed MM patients. Runx2 levels were significantly higher in patients who had a high risk of early disease-related death. The risk of death was determined by an existing gene expression profile test.
“This suggests that Runx2 levels in myeloma cells may be a gene predictor of a patient’s prognosis, good or bad,” Dr Yang said.
She and her colleagues also believe that targeting Runx2 expression could be a feasible strategy for treating aggressive MM.
rim of a bone spicule (pink)
New research indicates that multiple myeloma (MM) cells can “disguise” themselves as bone cells to elude the immune system, a trick that enables MM progression.
Investigators found evidence suggesting that MM cells mimic bone-marrow-resident cells by expressing bone-related genes, and this process is driven by overexpression of Runx2, a transcription factor that regulates bone formation.
“[R]unx2 overexpression can give multiple myeloma cells a bone-cell-like phenotype,” said Yang Yang, MD, PhD, of the University of Alabama at Birmingham.
“When the multiple myeloma cells come to the new bone sites, the bone immune cells think, ‘This is one of our neighbor cells,’ and therefore do not eliminate them. The bone immune cells do not recognize these cells as strangers.”
Dr Yang and her colleagues explained this phenomenon in Blood.
The investigators first conducted in vitro experiments and found that Runx2 expression in MM cells does not affect proliferation, but it does increase the cells’ invasiveness.
The team then used molecular genetic techniques to increase or decrease the expression of Runx2 in MM cells in vivo. They found that Runx2 overexpression promoted tumor growth and progression in mice. And mice with decreased Runx2 expression had less tumor growth and disease spread than control mice.
Further investigation revealed that Runx2 overexpression activates the Akt/β-catenin/survivin signaling pathway in MM cells. This is a different pathway than the one activated by Runx2 in solid tumors.
Downstream of the signaling pathway, Runx2 overexpression led to overexpression of bone-related genes, including genes expressed by osteoblasts, osteoclasts, and osteocytes.
Overexpression of Runx2 also enhanced secretion of soluble factors—including cytokines and growth factors—that aid tumor progression and metastasis.
In their final experiments, the investigators looked at Runx2 expression in human samples.
The team compared samples from 14 healthy bone marrow donors, 35 MM patients, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS). Runx2 levels were significantly higher in MM cells than in plasma cells from normal and MGUS samples.
The investigators also assessed Runx2 expression in a larger group of 351 newly diagnosed MM patients. Runx2 levels were significantly higher in patients who had a high risk of early disease-related death. The risk of death was determined by an existing gene expression profile test.
“This suggests that Runx2 levels in myeloma cells may be a gene predictor of a patient’s prognosis, good or bad,” Dr Yang said.
She and her colleagues also believe that targeting Runx2 expression could be a feasible strategy for treating aggressive MM.
Older cancer patients under-utilize advanced care planning
Photo courtesy of NCI
and Mathews Media Group
Survey results suggest the use of aggressive treatment at the end of life is on the rise among older cancer patients, and these patients often fail to employ advanced care planning measures.
Researchers reviewed nearly 2000 surveys of people whose loved ones died of cancer and found that, from 2000 to 2012, there was a 51% increase in reports that patients received “all care possible” at the end of life.
There was a 22% increase in power-of-attorney assignment over the same period, but the use of living wills and discussions about end-of-life preferences decreased slightly.
“Although more cancer patients are assigning power-of-attorney privileges to someone they know and trust to make their medical decisions when they can’t, this practice may be the least helpful among advanced care planning tactics because it may be least associated with treatment intensity at the end of life,” said Amol Narang, MD, of The Johns Hopkins Hospital in Baltimore, Maryland.
Dr Narang and his colleagues described this research in JAMA Oncology.
The team analyzed survey data from 1985 next-of-kin surrogates of cancer patients. The patients were older than 50 years of age, had taken part in the Health and Retirement Study, and died between 2000 and 2012.
The data included in-depth “exit” interviews conducted with the surrogates after a patient died. Seventy-nine percent of exit survey respondents said they were the primary decision-maker in the patient’s medical care.
The data showed a significant increase in power-of-attorney assignments, from 52% in 2000 to 74% in 2012 (P=0.03). But the use of living wills decreased slightly, from 49% to 40% (P=0.63), as did discussions about end-of-life preferences, which fell from 68% to 60% (P=0.62).
“We found that many cancer patients still do not communicate their preferences for end-of-life care, despite the potential benefits to patients’ quality of life and caregiver bereavement,” Dr Narang said.
Survey results also suggested a significant increase in the percentage of patients who received “all care possible” at the end of life, from 7% in 2000 to 58% in 2012 (P=0.004). But there was no significant change in the rates of terminal hospitalizations, which fell from 29% to 27% (P=0.70).
The researchers found that granting power-of-attorney privileges significantly decreased the odds that patients would die in the hospital as opposed to hospice or their homes (adjusted odds ratio [AOR]=0.70, P<0.05). However, granting power of attorney was not associated with a significant change in limiting or withholding treatment at the end of life (AOR=1.52).
On the other hand, patients who created living wills or had end-of-life discussions were significantly more likely than their peers to limit or withhold certain treatments. The AOR was 2.51 for living wills (P<0.001) and 1.93 for end-of-life discussions (P=0.002).
The researchers said they observed the same trends regardless of who completed the exit survey.
Dr Narang noted that this study had its limitations. The survey questions were subjective, answers could have been hampered by a respondent’s lapse in memory, and answers could be biased by a respondent’s desire to meet social norms.
“But we were looking at trends over time,” he said, “so respondents’ bias would not likely change over time.”
Photo courtesy of NCI
and Mathews Media Group
Survey results suggest the use of aggressive treatment at the end of life is on the rise among older cancer patients, and these patients often fail to employ advanced care planning measures.
Researchers reviewed nearly 2000 surveys of people whose loved ones died of cancer and found that, from 2000 to 2012, there was a 51% increase in reports that patients received “all care possible” at the end of life.
There was a 22% increase in power-of-attorney assignment over the same period, but the use of living wills and discussions about end-of-life preferences decreased slightly.
“Although more cancer patients are assigning power-of-attorney privileges to someone they know and trust to make their medical decisions when they can’t, this practice may be the least helpful among advanced care planning tactics because it may be least associated with treatment intensity at the end of life,” said Amol Narang, MD, of The Johns Hopkins Hospital in Baltimore, Maryland.
Dr Narang and his colleagues described this research in JAMA Oncology.
The team analyzed survey data from 1985 next-of-kin surrogates of cancer patients. The patients were older than 50 years of age, had taken part in the Health and Retirement Study, and died between 2000 and 2012.
The data included in-depth “exit” interviews conducted with the surrogates after a patient died. Seventy-nine percent of exit survey respondents said they were the primary decision-maker in the patient’s medical care.
The data showed a significant increase in power-of-attorney assignments, from 52% in 2000 to 74% in 2012 (P=0.03). But the use of living wills decreased slightly, from 49% to 40% (P=0.63), as did discussions about end-of-life preferences, which fell from 68% to 60% (P=0.62).
“We found that many cancer patients still do not communicate their preferences for end-of-life care, despite the potential benefits to patients’ quality of life and caregiver bereavement,” Dr Narang said.
Survey results also suggested a significant increase in the percentage of patients who received “all care possible” at the end of life, from 7% in 2000 to 58% in 2012 (P=0.004). But there was no significant change in the rates of terminal hospitalizations, which fell from 29% to 27% (P=0.70).
The researchers found that granting power-of-attorney privileges significantly decreased the odds that patients would die in the hospital as opposed to hospice or their homes (adjusted odds ratio [AOR]=0.70, P<0.05). However, granting power of attorney was not associated with a significant change in limiting or withholding treatment at the end of life (AOR=1.52).
On the other hand, patients who created living wills or had end-of-life discussions were significantly more likely than their peers to limit or withhold certain treatments. The AOR was 2.51 for living wills (P<0.001) and 1.93 for end-of-life discussions (P=0.002).
The researchers said they observed the same trends regardless of who completed the exit survey.
Dr Narang noted that this study had its limitations. The survey questions were subjective, answers could have been hampered by a respondent’s lapse in memory, and answers could be biased by a respondent’s desire to meet social norms.
“But we were looking at trends over time,” he said, “so respondents’ bias would not likely change over time.”
Photo courtesy of NCI
and Mathews Media Group
Survey results suggest the use of aggressive treatment at the end of life is on the rise among older cancer patients, and these patients often fail to employ advanced care planning measures.
Researchers reviewed nearly 2000 surveys of people whose loved ones died of cancer and found that, from 2000 to 2012, there was a 51% increase in reports that patients received “all care possible” at the end of life.
There was a 22% increase in power-of-attorney assignment over the same period, but the use of living wills and discussions about end-of-life preferences decreased slightly.
“Although more cancer patients are assigning power-of-attorney privileges to someone they know and trust to make their medical decisions when they can’t, this practice may be the least helpful among advanced care planning tactics because it may be least associated with treatment intensity at the end of life,” said Amol Narang, MD, of The Johns Hopkins Hospital in Baltimore, Maryland.
Dr Narang and his colleagues described this research in JAMA Oncology.
The team analyzed survey data from 1985 next-of-kin surrogates of cancer patients. The patients were older than 50 years of age, had taken part in the Health and Retirement Study, and died between 2000 and 2012.
The data included in-depth “exit” interviews conducted with the surrogates after a patient died. Seventy-nine percent of exit survey respondents said they were the primary decision-maker in the patient’s medical care.
The data showed a significant increase in power-of-attorney assignments, from 52% in 2000 to 74% in 2012 (P=0.03). But the use of living wills decreased slightly, from 49% to 40% (P=0.63), as did discussions about end-of-life preferences, which fell from 68% to 60% (P=0.62).
“We found that many cancer patients still do not communicate their preferences for end-of-life care, despite the potential benefits to patients’ quality of life and caregiver bereavement,” Dr Narang said.
Survey results also suggested a significant increase in the percentage of patients who received “all care possible” at the end of life, from 7% in 2000 to 58% in 2012 (P=0.004). But there was no significant change in the rates of terminal hospitalizations, which fell from 29% to 27% (P=0.70).
The researchers found that granting power-of-attorney privileges significantly decreased the odds that patients would die in the hospital as opposed to hospice or their homes (adjusted odds ratio [AOR]=0.70, P<0.05). However, granting power of attorney was not associated with a significant change in limiting or withholding treatment at the end of life (AOR=1.52).
On the other hand, patients who created living wills or had end-of-life discussions were significantly more likely than their peers to limit or withhold certain treatments. The AOR was 2.51 for living wills (P<0.001) and 1.93 for end-of-life discussions (P=0.002).
The researchers said they observed the same trends regardless of who completed the exit survey.
Dr Narang noted that this study had its limitations. The survey questions were subjective, answers could have been hampered by a respondent’s lapse in memory, and answers could be biased by a respondent’s desire to meet social norms.
“But we were looking at trends over time,” he said, “so respondents’ bias would not likely change over time.”